Results obtained during the last grant period reveal a number of long-term effects in fetal alcohol exposed (FAE) males compared to controls including: 1) alterations in circadian rhythms in adulthood, 2) decreases in arginine vasopressin (AVP) content in the bed nucleus of the stria terminalis (BNST) 3) a feminized water consumption pattern in adulthood which is reversed by prenatal testosterone treatment on days 18 and 19 of gestation, 4) decreased anatomical size of the supraoptic nucleus and 5) increased behavioral sensitivity to estrogen's stimulatory effect on locomotor rhythms. Several of our findings suggest an accelerated aging of the biological clock in the FAE male. Studies in this proposal are designed to test the hypothesis that fetal alcohol exposure will accelerate the age-related alterations in the control of circadian rhythms. Experiments are designed to test this aging hypothesis using both behavioral and hormonal rhythms. Other studies will test the hypothesis that alterations in circadian rhythms in response to aging or stress will be associated with changes in arginine vasopressin (AVP) and/or vasoactive intestinal peptide (VIP) expression in the suprachiasmatic nucleus. Studies of ethanol tolerance in FAE animals will be conducted to examine the functional significance of the reduced levels of AVP in the FAE brain. We have also included studies of an efficacious dose of testosterone to help counter the feminizing of ethanol on the sexual differentiation of the male brain. Finally, we have obtained results during this grant period indicating that the suppression or attenuation of the perinatal testosterone (T) surges by ethanol exposure during the last week of gestation is insufficient to significantly alter sex behavior of male or female rats in adulthood. Although this is recognized as the period of hypothalamic neurogenesis and differentiation in the rat, alcohol exposure during this period does not alter the size of the sexually dimorphic nucleus of the preoptic area (SDN) in either sex. Alcohol exposure does, however, produce a marked increase in the behavioral sensitivity of FAE males to estrogen-induced wheel running. These results suggest that additional factors may be involved in the long-term alterations in sexually dimorphic behaviors of FAE animals observed by ourselves and others. Therefore, we propose to focus our efforts in this area on brain aromatase activity in FAE animals. Overall, these studies are designed to elucidate the long-term behavioral effects of prenatal ethanol on circadian rhythms resulting from ethanol's actions on gonadal hormones during the perinatal period.